Jump to

Abstract

Introduction: Ventricular assist device (VAD) is an accepted treatment of end stage heart disease but the long-term success is limited by persistent thromboembolic events (TE). We hypothesized that rebound thrombin generation following heparin withdrawal is in part responsible for this increased risk of TE.

Methods: Thirty-one patients who were treated with left-sided VAD were enrolled to assess elevations in markers of thrombin generation (Prothrombin fragment F1.2) and neurological injury (S-100β) using ELISA. Anticoagulation activity of heparin was measured using aPTT. A twofold or greater increase in F1.2 levels above a baseline of ≤0.5 nM/mg protein was defined as a clinically important elevation. Biochemical evidence of neurological injury was obtained by analyzing daily plasma for S-100β, a marker of cerebral ischemia. TE was defined as evidence of a clinical (transient ischemic attack or clinical stroke) or biochemical (i.e. S-100 β ≥2x baseline) neurological event.

Results: There were 162 episodes of TE (13%) and 46 episodes of heparin withdrawal (3%) during 1365 patient-days of observation. Compared to all other days, F1.2 developed a significant increased on the day of heparin withdrawal (0.80 ± 1.43 vs. 0.39 ± 0.67; p<0.0004) and during a TE (2.26 ± 2.86 vs. 1.40 ± 2.03; p<0.0001). F1.2 (OR=1.23; 95% CI 1.03; 1.46; p=0.02) was a significant predictor of thromboembolic events after adjusting for the confounding variables, aPTT and blood flow in the VAD. Heparin withdrawal and a transient increase in F1.2 levels showed a 57% concordance in predicting TE.

Conclusions: Heparin withdrawal, which frequently precedes TE during VAD support, showed a strong concordance with bursts in thrombin production in predicting these events. This supports the use of the F1.2 assay as a surrogate of TE during this high risk period.